DISEASE/DRUG OF INTEREST: Cysticercosis/Albendazole
MOTIVATION AND BACKGROUND:
Cysticercosis is a tissue infection caused by ingesting tapeworm eggs that are present in undercooked pork [1]. The tapeworm larvae Taenia solium (T. solium) is responsible for the infection after ingestion when it will attach itself to the host’s stomach and grow into an adult [2]. The adult tapeworm will lay eggs and form cysts. Depending on the location and size of the cysts, they may not cause symptoms for years [2]. Although cysticercosis can be found globally and is one of the most common parasitic infections, it is most prevalent in developing Asian, African, and Latin American countries where sanitation of meat may not be as highly regulated [1,2]. The highest amounts of occurrences are throughout Mexico, Argentina, and Chile and although it is uncommon in the United States, those who are affected tend to be Hispanic American [3]. When the central nervous system is affected it causes neurocysticercosis which, if left untreated, is potentially fatal and with slower progress of medical advancements in the developing world, neurocysticercosis is more likely to remain untreated. Neurocysticercosis is primary cause of epilepsy in developing world and is typically treated with albendazole [2]. Symptoms of neurocysticercosis usually occur when the cysts begin dying because the brain tissue around the cyst swells and adds pressure to the affected area [1].
Figure 1. MRI scan revealing cysts formed in the brain
Figure 2. Life cycle of T. solium infection
TARGET INFORMATION: Albendazole works by targeting and inhibiting the tubulin alpha-3 chain (TUBA1A), a protein that binds 2 moles of GTP on the ends of the beta chain and the alpha chain [4]. TUBA1A combines with beta tubulin to form microtubules, determining cell shape and assisting cell organelle and vesicle movement using motor proteins [5]. According to its gene ontology, TUBA1A is also responsible for GTP binding, nucleotide binding, protein binding, GPTase and hydrolase activity [6].
DRUG INFORMATION:
Albendazole is a benzimidazole (combination of benzene and imidazole) which is used to inhibit the growth of parasitic worms, fungi, and viruses [7]. It is categorized as an anthelmintic and works by killing the tapeworms [8]. Albendazole should be avoided by pregnant women or plan on becoming pregnant as it can cause embryonic deformities [7]. Women who are breastfeeding are also advised to not take Albendazole [8]. Absorption of this drug may be increased by eating a meal higher in fats. The overall effectiveness of albendazole is heavily dependent upon the thickness of the cysts, the thicker the cyst, the longer it will take to see positive results [7]. Albendazole may cause side effects such as headaches, dizziness, and nausea which exacerbate the already present symptoms of neurocysticercosis [7]. Albendazole is normally prescribed for eight to twenty days and each dose should be taken at the same each day [8]. Medication should be stored at room temperature and contact with moisture should be avoided [8]. When albendazole is ingested the liver metabolizes it into albendazole sulfoxide which will further metabolize into albendazole sulfone [6]. It is important to note that not all patients may respond to the drug and it is possible that some patients may see negative results [8].
Figure 3. Schematic figure of Albendazole
REFERENCES:
Parasites – Cysticercosis. CDC 2012.
Kraft, R., Cysticercosis: an emerging parasitic disease. AAFP 2007, 76, (1), 91-96.
Zymberg, S. T., Neurocysticercosis. World Neurosurgery 2013,79, (2), S24.e5–S24.e8.
Cysticercosis/Albendazole
MOTIVATION AND BACKGROUND:
Cysticercosis is a tissue infection caused by ingesting tapeworm eggs that are present in undercooked pork [1]. The tapeworm larvae Taenia solium (T. solium) is responsible for the infection after ingestion when it will attach itself to the host’s stomach and grow into an adult [2]. The adult tapeworm will lay eggs and form cysts. Depending on the location and size of the cysts, they may not cause symptoms for years [2]. Although cysticercosis can be found globally and is one of the most common parasitic infections, it is most prevalent in developing Asian, African, and Latin American countries where sanitation of meat may not be as highly regulated [1,2]. The highest amounts of occurrences are throughout Mexico, Argentina, and Chile and although it is uncommon in the United States, those who are affected tend to be Hispanic American [3]. When the central nervous system is affected it causes neurocysticercosis which, if left untreated, is potentially fatal and with slower progress of medical advancements in the developing world, neurocysticercosis is more likely to remain untreated. Neurocysticercosis is primary cause of epilepsy in developing world and is typically treated with albendazole [2]. Symptoms of neurocysticercosis usually occur when the cysts begin dying because the brain tissue around the cyst swells and adds pressure to the affected area [1].
TARGET INFORMATION:
Albendazole works by targeting and inhibiting the tubulin alpha-3 chain (TUBA1A), a protein that binds 2 moles of GTP on the ends of the beta chain and the alpha chain [4].
TUBA1A combines with beta tubulin to form microtubules, determining cell shape and assisting cell organelle and vesicle movement using motor proteins [5]. According to its gene ontology, TUBA1A is also responsible for GTP binding, nucleotide binding, protein binding, GPTase and hydrolase activity [6].
DRUG INFORMATION:
Albendazole is a benzimidazole (combination of benzene and imidazole) which is used to inhibit the growth of parasitic worms, fungi, and viruses [7]. It is categorized as an anthelmintic and works by killing the tapeworms [8]. Albendazole should be avoided by pregnant women or plan on becoming pregnant as it can cause embryonic deformities [7]. Women who are breastfeeding are also advised to not take Albendazole [8]. Absorption of this drug may be increased by eating a meal higher in fats. The overall effectiveness of albendazole is heavily dependent upon the thickness of the cysts, the thicker the cyst, the longer it will take to see positive results [7]. Albendazole may cause side effects such as headaches, dizziness, and nausea which exacerbate the already present symptoms of neurocysticercosis [7]. Albendazole is normally prescribed for eight to twenty days and each dose should be taken at the same each day [8]. Medication should be stored at room temperature and contact with moisture should be avoided [8]. When albendazole is ingested the liver metabolizes it into albendazole sulfoxide which will further metabolize into albendazole sulfone [6]. It is important to note that not all patients may respond to the drug and it is possible that some patients may see negative results [8].REFERENCES:
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